title: Interaction between adipose tissue stromal cells and gastric cancer cells in vitro.
abstract: Adipose tissue exists in the gastric submucosa and subserosa. Thus, adipose tissue stromal cells (ATSCs), which include mesenchymal stem cells (MSCs), seem critical for the progression of gastric cancer but their interaction with the cancer cells is unknown. We demonstrated an interaction between these cells, using immunohistochemistry, Western blot and the collagen gel invasion assay system, in which the adenocarcinoma cells (well and poorly differentiated types, MKN28 and MKN45, respectively) were cultured on a ATSC-embedded or ATSC-non-embedded gel. ATSCs promoted the expression of the growth marker, proliferation cell nuclear antigen but inhibited that of the apoptosis marker, single-stranded DNA, in the cancer cell types. ATSCs accelerated the invasion of only MKN28 into the gel and promoted the expression of mitogen-activated protein kinase (MAPK, pERK-1/2) but decreased that of the molecularly targeted protein, HER2, in the cancer cells. ATSCs did not affect the expression of the prostaglandin biosynthetic enzyme cyclooxgenase-2 (COX-2) in the cancer cells. The COX-2 inhibitor celecoxib did not affect the morphology or invasion of the cancer cells. The cancer cell types in turn promoted the display of the myofibroblast marker, α-smooth muscle actin, whereas they decreased that of some MSC markers, e.g., CD44 and CD105, in ATSCs. The data suggest that (1) ATSCs influence the progression of gastric cancer by increasing their growth/invasion and decreasing their apoptosis through MAPK activation in a COX-2-independent way; (2) ATSCs adversely affect HER2-targeted therapy; (3) the cancer cells induce the cancer-associated myofibroblast phenotype in ATSCs.
authors.affiliation: Department of Pathology & Microbiology, Faculty of Medicine, Saga University, Nabeshima, Saga, Japan. nnomoto@niu.ac.jp
authors.forename: Namie
authors.initials: N
authors.lastname: Nomoto-Kojima
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Aoki
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Uchihashi
authors.forename: Aki
authors.initials: A
authors.lastname: Matsunobu
authors.forename: Eisuke
authors.initials: E
authors.lastname: Koike
authors.forename: Akifumi
authors.initials: A
authors.lastname: Ootani
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Yonemitsu
authors.forename: Kazuma
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Toda
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis; D009077:Mucins / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D020930:MAP Kinase Kinase Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009077:Mucins; D018719:Erb-b2 Receptor Tyrosine Kinases